5-Aminolevulinic acid is widely present in the biosphere as a metabolic intermediate in the pigment biosynthetic pathway biosynthesizing tetrapyrrole compounds (such as vitamin B12, heme, and chlorophyll) and plays important roles in vivo. 5-Aminolevulinic acid is biosynthesized in biological systems from glycine and succinyl CoA by means of a 5-aminolevulinic acid synthase or from glutamic acid through glutamyl tRNA and is converted into porphyrin compounds such as heme or chlorophyll by means of metabolism following 5-aminolevulinic acid dehydratase. This 5-aminolevulinic acid is highly degradable and substantially does not remain in the environment and is therefore expected to be applied to a variety of industries (Patent Literatures 1 and 2).
A method using a variety of photosynthetic bacteria, in particular, bacteria belonging to Rhodobacter or variants thereof is known as the method for producing 5-aminolevulinic acid or a salt thereof using microorganisms (Patent Literatures 3 and 4). In addition, for example, a method of culturing such microorganisms under oxygen-limited conditions (Patent Literature 5), a method using a variant producing 5-aminolevulinic acid under moderated conditions of the oxygen-limited conditions (Patent Literature 6), and a method using an established oxygen condition (Patent Literature 7) have been reported.
Although culturing conditions have been reported as described above, there have been no reports on culture media and productivity improvers for increasing productivity excepting the description on the amount of iron (Patent Literature 6).
In general, 5-aminolevulinic acid or the salt thereof produced by microorganism culture described above can be optionally isolated and purified in accordance with a usual method such as ion exchange chromatography or extraction. In order to achieve high purification, a method for isolating 5-aminolevulinic acid from a culture solution using a cation exchange resin is known (Patent Literature 8). The purification of 5-aminolevulinic acid using a cation exchange resin is affected by a by-product, 5-amino-4-hydroxypentanoic acid of Formula (1). That is, since this 5-amino-4-hydroxypentanoic acid has a pKa value and a pI value that are very close to those of 5-aminolevulinic acid, in purification by ion exchange chromatography, 5-amino-4-hydroxypentanoic acid and 5-aminolevulinic acid compete for exchange groups of the ion exchange resin. Accordingly, achievement of high purification of 5-aminolevulinic acid requires use of an ion exchange resin in a large amount relative to the amount of 5-aminolevulinic acid passing through the resin. Therefore, inhibition of the accumulated amount of 5-amino-4-hydroxypentanoic acid in the culture solution is effective for increasing the efficiency of high purification of 5-aminolevulinic acid by ion exchange chromatography.
